The studies described in this proposal are designed to evaluate the effect of parity and HLA alloantigens, and their interaction if any, in the course and prognosis of rheumatoid arthritis. Recent studies have demonstrated an association of nulliparity with an increased risk of RA. For women with established RA, pregnancy is associated with remission or improvement of disease in 70% of cases; however, the postpartum period is almost invariably accompanied by disease flare. Thus events related to parturition are known to both affect susceptibility to RA and to influence the on going disease course. Despite these observations, and general agreement that the prognosis of RA is worse for women than men, knowledge of the effect of parity on RA prognosis is lacking.in 1977 Stastny first described an association of HLA-Dw4 with RA susceptibility and accumulating evidence now suggests that HLA class II antigens also influence prognosis of RA. Recent studies have shown that severe disease may correlate better with allelic variants of class II genes defined using DNA-based typing techniques. Testing using these techniques is currently feasible for clinical purposes. However, the spectrum of disease in RA patients is best described as protean and the prognostic value of specific class II alleles has not been tested in incident RA cases. The current studies propose to evaluate reproductive and immunogenetic factors in the prognosis of recent onset RA in women by follow-up of incident cases from a prospective case-control study. Whether these factors are at interactive in disease prognosis is unknown and will also be examined. Lastly, pregnancy-induced remission of RA, first reported by P.S. Hench in 1938, potentially presents a biologic interface of immunogenetic and reproductive factors. We have recently shown an association of disease improvement during pregnancy with fetal-maternal disparity for HLA class II antigens. The final aim of this proposal is to test the hypothesis that maternal humoral response to class II antigens contributes to pregnancy- induced disease amelioration. For this purpose pregnancies in RA patients will be studied prospectively.